PubMed · 1310255
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D B Bach, R G Kennedy, D Hurlbut, C A McLean, M F Levin, P L Munk, A D Vellet. 1992. Obstructive jaundice.. https://pubmed.ncbi.nlm.nih.gov/1310255/
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Three types of expandable metallic stents were used to relieve obstructive jaundice in 59 patients. They consisted of 3 cases with benign stricture, and 56 with malignant obstruction including 28 of cholangiocarcinoma, 17 of pancreatic carcinoma, 9 of lymph node metastases, and 2 of gall bladder carcinoma. The median age of patients was 68.9 years. Of 56 cases with malignant obstruction, 51 cases were able to remove external drainage catheter. In these 51 cases, 35 patients died, and 16 are still alive. No significant difference was noted in the incidence of stent destruction or migration in three types of stents. The average survival period was 189.9 days in 35 patients who died after withdrawal of external drainage. Twenty-three of 35 patients had no recurrence of obstructive jaundice. Sixteen patients with malignant obstruction are still alive and have been observed for 22 to 764 days. The 30 day mortality rate was 6.8%. Three cases of acute cholecystitis were noted after procedure. It is warranted to say that endoprostheses using expandable metallic stents will be the major treatment of choice for biliary obstruction because of long term patency and low complication rate.
Monoclonal antibodies (MAbs) often distribute nonuniformly in tumors. In part, that observation reflects intrinsic heterogeneity within the tumor; in part, it reflects poor penetration through tumor substance. Several years ago, we proposed the "binding site barrier" hypothesis (J.N. Weinstein, R.R. Eger, D.G. Covell, C.D.V. Black, J. Mulshine, J.A. Carrasquillo, S.M. Larson, and A.M. Keenan, Ann. NY Acad. Sci., 507: 199-210, 1987; K. Fujimori, D.C. Covell, J.E. Fletcher, and J.N. Weinstein, Cancer Res., 49: 5656-5663, 1989), the idea that antibodies (and other ligands) could be prevented from penetrating tumors by the very fact of their successful binding to target antigen. Calculations suggested that this might be a significant factor in the therapy of even microscopic nodules. The higher the affinity and the higher the antigen density, the greater the barrier. Here, we provide direct experimental evidence of such a barrier to the percolation of D3 MAb through intradermally implanted line 10 carcinoma of guinea pigs. After affinity purification using glutaraldehyde-fixed line 10 cells, the D3 had an average immunoreactivity of 88%, a binding constant of 1.6 +/- 0.3 (SEM) x 10(10) M-1, and saturation binding of 355,000 +/- 15,000 molecules/cell. Using a combination of double-label autoradiography and double-chromagen immunohistochemistry, we determined simultaneously the distribution of (a) i.v. injected D3 MAb; (b) coinjected isotype-matched control IgG (BL3); (c) D3 antigen; (d) blood vessels. The previously developed mathematical models aided in the design of these experiments. Double immunochemical staining of the tumors showed antigen-rich patches 100-800 microns across, surrounded by blood vessels. At a low MAb dose (30 micrograms), binding to antigen severely hindered penetration into antigenic patches as small as 200 microns, even at 72 h. Explanation of this finding by a physical barrier was ruled out by the observation that BL3 distributed uniformly in the same patches. At a higher dose (1000 micrograms), the binding site barrier could be partially overcome. The same general principles of micropharmacology may apply to biological ligands other than antibodies, including those secreted by genetically modified cells.
Nonhematopoietic hepatic neoplasms (n = 25) were diagnosed in 21 cats during a 5.5-year period. Thirteen of the neoplasms were benign bile duct adenomas and 12 were malignant, 6 of which were bile duct adenocarcinomas. All cats were greater than or equal to 10 years old, and 14 were male. Main clinical signs were anorexia and lethargy, and 15 of 21 cats had hepatomegaly. All 21 cats were feline leukemia virus-test negative. Although there was a trend toward high activities of serum alanine transaminase and aspartate transaminase, neither clinical signs nor enzyme activity were specific for diagnosis of hepatic neoplasia in the cats of this study.